The microtubule cytoskeleton is an important component of the vertebrate photoreceptor. It contributes to the structural integrity of the photoreceptor cell, it mediates the vectorial trafficking of outer segment precursors via the connecting cilium, and it may be a critical target for proteolysis during retinal degeneration. In order to understand the function of the microtubule cytoskeleton, it is necessary to discover the complete repertoire of microtubule-associated proteins (MAPs) and to elucidate their structures. The objective of this project is to identify and characterize photoreceptor MAPs. It is the hypothesis of this project that there exist heretofore unidentified photoreceptor MAPs. This project will employ a directed strategy based upon the unique ability of all MAPs to bind to microtubules with significant affinity. The photoreceptor MAPs will be characterized by comparing them to known MAPs (originally characterized from non-retinal sources) and by testing whether any of the MAPs displays characteristics common to microtubule motor proteins (dynein or kinesin). Monoclonal antibodies will be raised and characterized against the novel photoreceptor MAPs. These antibodies will be utilized to localize each MAP in the retina. The project is a first-time entry into the field of vision research by a laboratory with extensive experience in the identification and characterization of MAPs structural MAPs and microtubule motors) in other systems. The proposal outlines an innovative venture because it will apply a novel procedure to attempt to discover heretofore unidentified photoreceptor MAPs. If interesting MAPs are discovered, then much work beyond the single year of the Pilot Project will be required to characterize them and to determine their function in normal and diseased tissue, and the results obtained during the Pilot Project will serve as the basis for future, more extensive studies. On the other hand, if the strategy reveals no novel MAPs, then his would also be an important finding which should be shared with others who might contemplate similar approaches in their study of the photoreceptor.